Effects of lercanidipine on coronary reactivity and myocardial remodeling in transition to heart failure in cardiomyopathic hamsters.

Abstract

AIM:

Lercanidipine is a new vasoselective dihydropyridine calcium channel blocker with a short plasma half-life, long duration of action, and demonstrated cardioprotective properties. We hypothesized that it might be effective at attenuating the adverse impact observed on the coronary compartment and myocardium in the transition phase to heart failure in the UM-X7.1 cardiomyopathic (CM) hamster.

METHODS:

The effects of 4-month exposure to lercanidipine 3 and 10 mg/kg (daily oral administration) were evaluated in 150-day-old CM hamsters and in age-matched normal hamsters. Coronary reactivity (reactive hyperemia to 30-s coronary occlusion) and the response to the administration of acetylcholine (100 nmol/L) and sodium nitroprusside (1 micromol/L) were assessed monthly, using the isolated perfused heart model. The left ventricular chamber dilatation index and wall thickness, myocardial fibrosis and myocardial capillary density (papillary muscle) were estimated in selected subgroups at monthly intervals.

RESULTS:

High-dose lercanidipine had beneficial effects on coronary dysfunctions: at month 4 of the treatment period, reactive hyperemia to short duration ischemia was improved, as was the endothelium-dependent vasodilator response (acetylcholine=68 %+/-16 % vs 11 %+/-5 % in untreated CM hamsters, P<0.05) and endothelium-independent vasodilator response (sodium nitroprusside=36 %+/-5 % vs 22 %+/-12 % in untreated CM hamsters, P<0.05). Capillary density averaged 10,879+/-474 capillaries per mm2 in papillary muscle from normal hamsters; this value did not change over time in normal hamsters and was not affected during the transition phase to heart failure in CM hamsters. Lercanidipine preserved myocardial capillary density in these conditions. Chronic exposure to lercanidipine had no impact on myocardial remodeling observed in CM hamsters.

CONCLUSION:

Lercanidipine had a beneficial impact on the coronary compartment in the transition phase to heart failure in a model of dilated cardiomyopathy.

• Authors: Julie Massicotte, Antoine Viens, Ming-Hui Yao, Amedeo Leonardi, Giorgio Sironi, Hongbo Wang, Louis Dumont
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 24 Issue 3 Pg. 199-206 (Mar 2003) ISSN: 1671-4083 [Print] United States
• PMID: 12617766 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channel Blockers
• Cardiotonic Agents
• Dihydropyridines
• Vasodilator Agents
• Nitroprusside
• Acetylcholine
• lercanidipine

Topics

• Acetylcholine (pharmacology)
• Animals
• Calcium Channel Blockers (pharmacology)
• Capillaries (pathology)
• Cardiomyopathies (pathology)
• Cardiotonic Agents (pharmacology)
• Cricetinae
• Dihydropyridines (pharmacology)
• Female
• Heart Failure (pathology)
• Male
• Mesocricetus
• Myocardium (pathology)
• Nitroprusside (pharmacology)
• Vasodilator Agents (pharmacology)
• Ventricular Remodeling (drug effects)